PwC and IPHA
Pathfinder Study for the Adoption of Cell and Gene Therapies in Ireland
May 2021 2 | The Pathway to CGT Adoption in Ireland
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Vision Statement
CGTs are usually one-time treatments that can add months, Our research led to sometimes years, to a patient’s life, replacing a lifetime of treatment. The study argues that, although the upfront cost three major findings of CGTs is significant, they could reduce the long-term direct and indirect costs of chronic treatment for certain illnesses, Cell and Gene Therapies (CGTs) have achieved improving patient outcomes. Our analysis cites cancer, 1 groundbreaking clinical results in a number of haemophilia and spinal muscular atrophy Type 1 as diseases therapeutic areas, significantly improving the where CGTs could yield crucial economic and clinical standard of care for patients with serious illnesses. upsides.
For certain degenerative diseases, the European We hope the study can inform the healthcare policy debate 2 Medicines Agency has approved CGTs that can in the near term. CGTs bring clear clinical benefits but they halt the progression of the disease. Historically need to be integrated into the care pathway in a financially treatment for many of these illnesses has been sustainable way. How the health system pays for them, and supportive rather than curative. how their value is measured in the community, are areas for further consideration. Now is the time to start a dialogue with A re-think of the reimbursement model is key stakeholders. Innovation moves at pace and so must our 3 required to ensure Irish patients can access new policymaking. medicines and to encourage further innovation in new medicines and therapies. This will require multi-stakeholder collaboration. 4 | The Pathway to CGT Adoption in Ireland Plotting The Adoption Path
In medicine, there is a revolution happening that is changing The goal is fully aligned with Sláintecare’s vision for world- • Explore novel reimbursement models for CGTs to ensure how we treat, and potentially cure, some of the most class standards of care in Ireland. The study recognises broad access and value for money for Irish patients; and, devastating of diseases. Cell and gene therapies, or CGTs, that current reimbursement models should be adapted for • Continue to invest in facilities and staff to ensure a are a new frontier in science that holds the prospect of CGTs. The delivery of both clinical benefit and value for smooth national rollout of CGTs, exploring the creation of significantly modifying the trajectory of disease and, in the money in CGT adoption needs to be explored through novel ‘centres of excellence’ at certain hospital sites and allied process, changing the lives of patients for the better. reimbursement pathways. investment in training and engagement for clinicians and Cell therapy replaces diseased, faulty or missing cells with Across the world, CGTs are either in use or in research patients. healthy versions. Gene therapy helps correct faulty DNA for the treatment of a range of disease areas, including The study shows that CGTs have achieved ground-breaking to cure genetic diseases. These breakthrough treatments, cancer, blood disorders, ophthalmology, neurology, and results in several therapeutic areas, including in cancer, aiming to treat, prevent and potentially cure genetic and musculoskeletal, metabolic and endocrinological conditions. degenerative diseases (inherited retinal disease), neurological acquired diseases, are, so far, not available in Ireland. In this In the US, the medicines regulator, the Food and Drug diseases (spinal muscular atrophy) and haemophilia. CAR-T, study, we outline a set of recommendations that are intended Administration, expects to approve between 10 and 20 new a form of cell therapy, is used to treat leukaemia, lymphoma to add urgency to the cell and gene therapy adoption effort. CGTs between now and 2025. Europe’s medicines regulator, and multiple myeloma. It is available in more than 15 EU Considered policymaking happens through dialogue - but the European Medicines Agency, has approved CGTs for countries but not yet in Ireland. The Treatment Abroad action must swiftly follow. Patients cannot wait. leukaemia, lymphoma, retinitis pigmentosa, spinal muscular Scheme covers treatments not available in Ireland or where atrophy and Crohn’s disease. Together, thousands of patients there is delay in getting a treatment. In 2019, the scheme The originator industry in Ireland, through the Irish in Ireland could benefit from CGTs for these diseases if they cost the State €54 million, according to the Health Service Pharmaceutical Healthcare Association (IPHA), were reimbursed locally. Executive. commissioned the global professional services firm, PwC, to carry out a pathfinder study on the adoption of CGTs by the The study makes several recommendations that would The evolution of science, especially our understanding of the health services. This study is the industry’s response to an help patients to access potentially life-changing therapies, causes of disease, is beginning an exciting era for medicines. urgent public healthcare need. including: Innovation is transforming standards of care, moving towards more targeted treatments and enabling improvements in In undertaking the study, IPHA asked PwC to gather experts’ • The development of a CGT adoption policy, guided by patient, health and social outcomes. Clinical options for perspectives. We interviewed a range of leaders across a White Paper led by the Department of Health, which patients are widening - but we must work together to find clinical care, regulatory affairs, patient advocacy and the draws together proposals for tackling the related strands ways of sustainably adopting them in the health services. biopharmaceutical industry. We examined globally available of assessment, access and reimbursement; That will take joint working - and there is no time to lose. clinical data on CGTs. • Improve the information infrastructure and implement new We look forward to the journey ahead. The goal of the study is to prompt the development of policy initiatives to enable real-world evidence collection a White Paper, enabled by structured cross-stakeholder for key disease areas likely to benefit from CGTs in the dialogue, ideally led by the Department of Health. That would short term and start planning for a broader rollout of CGTs ultimately yield a national policy on the adoption of CGTs in in other areas in the medium term; Ireland. This is important for patients and for their clinicians. 5 | The Pathway to CGT Adoption in Ireland
“This study moves “CGTs are “Standard treatment Ireland closer to revolutionising since the 1970s has having a policy on medicine. They often been intravenous the adoption of offer better treatment infusions of the CGTs by the health options for life- missing clotting services. That will take threatening illnesses. In factor. Now, science dialogue and careful some cases, they have is offering potentially planning - but, on the potential to cure breakthrough the basis of clinical diseases altogether. treatments for evidence so far, it is Gene therapy for haemophilia. Last the right thing to do ocular diseases is March, the first for better patient care, a significant area of Irish person with aligned with the goals of Sláintecare. We must research, especially since many rare, blinding haemophilia B was treated with gene therapy as be open to adopting new innovations affordably retinal diseases do not have treatments now. part of a clinical trial. It was a landmark moment and at pace in our health services. This study We can work on the eye more easily because for the haemophilia community in Ireland. We is an industry contribution to an urgent public it is an enclosed organ with elements of are moving closer to making gene therapy a policy need. We were keen to gather experts’ immune privilege and several identified genetic possible functional cure for haemophilia. This perspectives, including from doctors, patients mutations that could be targeted. The way study is an important signpost on a journey and our own industry. We hope the study can forward is to have a policy on CGTs that makes towards the adoption of approved CGTs in the prompt structured dialogue in the form of a it possible for doctors to prescribe approved health services. The impact on patients’ lives cross-stakeholder forum, led by the Department CGTs for their patients locally.” could be transformational.” of Health, which would ultimately yield a national policy on the adoption of CGTs in Ireland. This is important for patients and for Professor David Keegan Brian O’Mahony their clinicians. It recognises, too, that current Mater Misericordiae University Hospital, Dublin CEO, Irish Haemophilia Society reimbursement models will not work for CGTs. We need to explore how we can deliver both clinical benefit and value for money from CGT adoption.”
Oliver O’Connor CEO, IPHA 6 | The Pathway to CGT Adoption in Ireland
High-Level A number of urgent steps can be taken to ensure Irish patients gain access to innovative and potentially Recommendations life-changing therapies over the coming years.
Current situation Recommendation
Cell and Gene The current assessment process need to be updated to account for A CGT adoption policy, guided by a White Paper led by the Therapy Assessment new therapeutic categories like CGTs, ensuring that the scope and Department of Health, which draws together proposals for Framework timeline of assessments are suitable and transparent tackling the related strands of assessment, access and reimbursement
Novel Reimbursement The current reimbursement process limits Irish patient access to Introduce novel reimbursement models for CGTs to ensure Models innovative treatments such as CGTs broad access and value for money for Irish patients
Efficacy data The infrastructure to collect long-term healthcare data for the use Improve the data infrastructure for key disorders likely to of outcomes-based reimbursement is underdeveloped and lacking benefit from CGTs in the short term and start planning for a key capabilities broader rollout in other areas in the medium term
Expertise and While Irish centres of excellence are in place to adopt cell and gene Continue to invest in facilities and staff while ensuring training Resources therapies, investment in key enablers for delivery is required to and engagement with clinicians and patients to allow for a improve access and ensure best possible outcomes smooth national rollout of CGTs 7 | The Pathway to CGT Adoption in Ireland
Statement of Methodology This report was created based on independent desk research, interviews with healthcare professionals and patient groups, and interviews to gain industry insights
1
Independent analysis of available research and data, such as clinical trial Independent results, studies by patient advocacy Analysis groups and medical journal articles of Available Research and Efficacy Data
Interviews with healthcare professionals to discuss the potential of CGTs in their treatment area, and the readiness of the Irish healthcare Pathfinder system to deliver these treatments Insight of Report Interviews with key players Interviews with patient advocacy Healthcare in the biopharmaceutical groups to understand the Professionals Industry industry to gain their current standard of care for Irish perspective on the current patients, patient registries and the and Patient Perspective landscape for CGTs in Ireland potential of CGTs in their area Advocacy Groups 2 3 8 | The Pathway to CGT Adoption in Ireland Report Contents
Section 1 • An Overview of Cell and Gene Therapies 09
Section 2 • The Efficacy of Cell and Gene Therapies and their Impact on Patients 15 • Cancer 16 • Degenerative Diseases: Inherited Retinal Diseases 18 • Neurological Diseases: Spinal Muscular Atrophy 19 • Haemophilia 20 • Patient Perspectives 21
Section 3 • The Drug Approval Process in Ireland 24 • The Economic Case for Cell and Gene Therapies 25 • Reimbursement Options 26 • Recommendations to Improve the CGT Landscape in Ireland 28
Appendix 32 9 | The Pathway to CGT Adoption in Ireland Section 1: Overview of Cell and Gene Therapies
• The Evolution of Medical Treatments • Overview of Cell and Gene Therapies • Cell and Gene Therapies Under Development • Approved Cell and Gene Therapies 10 | The Pathway to CGT Adoption in Ireland
A Timeline of Medical Innovation Medical innovation has progressed from a “one-size-fits-all” approach towards precision medicine, taking into account variability in genetics, environment and the lifestyle of patients
One-size-fits-all approach Precision treatments
The Past The Present The Future
Combinations of cell One-size-fits-all Progress in therapies and new treatments (e.g. treatments that technologies such as broad spectrum harness the body’s nanotechnology and antibiotics) immune system to 3D printing (e.g. 3D fight disease (e.g. Omics, a field of study in printed organs) immuno-oncology biological sciences, and treatments) molecular technologies that harness the various types of molecules within a cell (e.g. CRISPR)
Rise of rationally designed therapies based on high throughput screening Serendipitous discovery that allows for much of treatments for major Innovative vaccines (e.g. mRNA more specific targeting of Cell and Gene Therapy: disorders (e.g. antibiotics, treatments vaccines for oncology) antipsychotics) Precision medicine, aiming to treat, prevent and potentially cure genetic and acquired diseases
Source: PwC Research 11 | The Pathway to CGT Adoption in Ireland
Cell and gene therapies aim to treat, How are Cell Cell and Gene Therapies are prevent and potentially cure genetic and acquired diseases such as cancer, and Gene a New Category of Therapy blindness and neurological diseases Therapies different What are Cell and Gene Therapies? from more Cell therapy and gene therapies are overlapping fields of biomedical treatment which aim to either treat or alleviate acquired diseases and diseases of a genetic origin. Cellular therapies derive changes through the introduction of new cells as the therapy, whereas gene therapies target errors in conventional the body’s genetic code that cause illness1. treatments? Cell Therapy Gene Therapy Conventional Treatments Cell therapy aims to introduce new, healthy cells into a patient’s Direct Direct gene delivery Modification of cells in Cell-Based • Uses small molecules, body to replace diseased or missing T-cells. One of the most via injection in vivo culture (ex vivo), followed by advanced forms of cell therapy is CAR-T treatment for different Delivery to target tissues cell expansion and injection Delivery peptides, proteins types of blood cancer. • Long-term therapy Therapeutic Therapeutic • Manage or treat symptoms Example - The CAR-T Process transgene transgene
Leukapheresis Manufacturing process Infusion with Collect patient’s Isolate and activate T-cells a therapeutic The therapeutic Vs. white blood cells agent transgene is packaged Infuse same The therapeutic into a delivery patient with transgene vehicle such as Cell and Gene Therapy engineered is packaged a virus into a delivery • Uses DNA, RNA and cells T-cells Engineer T cells vehicle such as a virus • One-time treatment with CAR gene The therapeutic transgene is introduced into a delivery • Aims to halt or modify the cell such as a stem cell that is often derived progression of a disease from the patient ...and injected into the patient Grow and expand number of T-cells Target organ The genetically (e.g. liver) ...and readministered to the patient modified cells (e.g. stem cells) are multiplied in the laboratory
Source: PwC Research, Novartis 12 | The Pathway to CGT Adoption in Ireland
Cell and Gene Therapies Under Development Cell and Gene Therapies have the potential to treat a broad range of diseases, from cancer to diabetes, and to revolutionise medicines
Cell and Gene therapies are being explored for the treatment of disease across a wide range of Therapeutic Areas2
Overview of main disease brackets with CGTs approved or in clinical trials*
Metabolic and Cancer3 Blood Disorders4,5 Ophthalmology6,7 Neurology8, 9, 10 Musculoskeletal11, 12 Endocrinology13, 14, 15, 38
100 Leukaemia (5,765) 75+25Haemophilia A (214) 100 Retinitis pigmentosa 100 Spinal muscular 50+50Duchenne muscular 1000 Crohn’s disease (1,244) atrophy (55) dystrophy (110) (11,200) 100 Lymphomas (11,036) 75+25Haemophilia B (60) 25+ 75 Age-related macular 50+50Huntington’s 50+50Osteoarthritis 100 Metachromatic 75+25Multiple myeloma 75+25Sickle cell degeneration disease (700) (400,000) leukodystrophy (9) (1,879) disease (350) (110,000) 50+50Multiple 50+50X-linked myotubular 50+50Diabetes (195,000) 50+50Breast cancer sclerosis (8,000) myopathy (-) (43,750) 50+50Gaucher’s 50+50Parkinson’s disease (11) 50+50Ovarian cancer disease (12,000) (3,187)
Numbers in brackets represent the estimated Latest development stage achieved to date: 100 Approved by EMA 75+ 25 Phase III Trials 50+ 50 Phase I/II Trials 25+ 75 Pre-clinical number of Irish patients with this illness
Note: *This is a sample of illnesses for which CGTs are currently approved or under development. Cell and gene therapy research is underway for a vast number of other illnesses. Number of patients with cancer is defined as the number of cancer survivors on 31/12/2018. Source: American Society of Gene and Cell Therapy, National Cancer Registry Ireland, Rare Disease Taskforce, The Irish Times, Journal of Public Health, Fighting Blindness, Central Statistics Office, Health Service Executive, Muscular Dystrophy Ireland, Irish Health Clinic, Irish Society for Colitis and Crohn’s Disease, Irish Medical Times. 13 | The Pathway to CGT Adoption in Ireland
Approved Cell and Gene Therapies Treatment Certain CGTs have been approved by the EMA and the FDA, and are now Abroad available in many European countries, but not yet in Ireland Scheme
Key: Countries that have approved Cell and Gene The Treatment Abroad Scheme CGTs approved for reimbursement (TAS) was introduced to ensure CGTs not yet approved Therapies for reimbursement that all EU patients have access to the same level of medical expertise and treatments regardless of where they live. Irish patients are currently travelling Irish patients can access medical to the UK to receive treatments that are not available CAR-T treatment in Ireland, or not available in the on the Treatment timeframe required. Unproven Abroad Scheme or experimental treatments are not covered by the scheme and paediatric patients are among the largest cohorts for whom As of May 2021, no TAS referrals are made. CGTs have been reimbursed in Ireland The cost of the Treatment Abroad Scheme and related CGTs were first approved expenditure was €54 million in by the EMA for Cancer, 201918, up 48% on 201619, as Eye Disease and Irish patients increasingly require Gastroenterology in 2018 cutting-edge treatments that and Spinal Muscular are available elsewhere in the Atrophy in 202017 European Union. CGTs were first approved by the FDA It is not known how many Irish CGTs have been approved for Cancer and Eye patients have not been able for Cancer in 2021 Disease in 2017, and to access treatment, including for Spinal Muscular CGTs, via the Treatment Abroad Atrophy in 201916 Scheme.
Source: FDA: Approved Cellular and Gene Therapy Products, 2021; Advanced therapy medicinal products: Overview - European Medicines Agency, 2021; Health Service Executive - Annual Reports, 2016 and 2019; PwC Research. 14 | The Pathway to CGT Adoption in Ireland Section 2: The Efficacy of Cell and Gene Therapies and their Impact on Patients
• Cancer • Degenerative Diseases: Eye Disease • Neurological Diseases: Spinal Muscular Atrophy • Haemophilia • Patient Perspectives 15 | The Pathway to CGT Adoption in Ireland
The Efficacy of Cell and Gene Therapies Cell and Gene Therapies have achieved groundbreaking results in a number of therapeutic areas, significantly improving the standard of care for patients with serious illnesses
Cancer Degenerative Diseases - Inherited Retinal Disease
• CAR-T is a form of cell therapy used to treat certain cancers such as leukaemia, • Cell and gene therapies have succeeded in stopping disease progression and lymphoma and multiple myeloma. preserving vision. • Two CAR-Ts for three indications have been approved by the European • The standard of care for this disease has moved from supportive towards Medicines Agency and reimbursed in 15+ EU countries, but are not available in preventing damage to cells that cause blindness in the first place. Ireland. • CAR-Ts are currently used as a final line of treatment where patients have failed to respond to all other cancer treatments. They have been shown to be effective across a range of cancers in placing a percentage of these patients back into long-term remission who would otherwise be placed into palliative care.
Neurological Diseases - Spinal Muscular Atrophy Haemophilia
• Spinal Muscular Atrophy (SMA) is a rare genetic neuromuscular disease caused • Haemophilia is a genetic condition where the blood does not clot properly, by a lack of a functional SMN1 gene. leaving patients at increased risk of heavy bleeding episodes and internal bleeding. • SMA results in the progressive and irreversible loss of motor neurons, affecting muscle functions, including breathing, swallowing and basic movement. • Preliminary data on patients treated with gene therapy for haemophilia have shown they may only require a single treatment. They have achieved continuous • If left untreated, SMA Type 1 leads to death or the need for permanent normal levels of clotting, experienced no bleeding episodes, and have been able ventilation by the age of two in more than 90% of cases. to live a far more active lifestyle. 16 | The Pathway to CGT Adoption in Ireland
Cancer CAR-T therapy has the potential to improve overall survival of patients with blood cancer where all other available treatment options have failed
Overview Clinical Efficacy Patient Impact
Cell therapy, or ‘CAR-T’ Efficacy of Cell Therapy in Efficacy of Cell Therapy in • About 10% of patients with blood cancer will not respond to currently therapy, is used to treat Children and Young Adults some Lymphoma Sub-Types available treatment options and will relapse. CAR-T has the potential certain blood cancers in with ALL to place these patients back into remission. which patients have failed to 4x more likely 2.5x more • A small number of patients can currently receive CAR-T treatment respond to all conventional 100 100 to respond to likely to survive abroad through the Treatment Abroad Scheme. This requires patients treatment options. They treatment 3 years post and their families to make multiple trips abroad for treatment, with a have been approved for the 80 80 treatment severely compromised immune system. treatment of blood cancer 81% in children, young adults, International Key Opinion Leader views on the current patient and adults, and are currently 60 60 experience available in many European countries. 40 40 47% “Ireland is well behind the curve in terms of cellular therapy. We are CAR-T is administered as a close to the last country in Europe to reimburse CAR-T therapies.” 20 20
one-time treatment in which a Overall Survival Rate % Overall Response Rate % patient’s T cells are removed 20% 20% “We’ve done everything we can, we’ve onboarded, we’ve done from their blood and modified 0 0 training, we’re fully up to speed. All we need to make it happen for in a lab so they will attack 3 months after treatment 3 years after treatment Irish children is to be given the funding to do it. We don’t believe it’s cancer cells. rocket science anymore, this is now part of frontline protocol.” With CAR-T therapy Without CAR-T therapy
• In children, three months after CAR-T infusion, 81% of CAR-T “There is a rapid increase in CAR-T being used in children and young patients were in remission, as opposed to 20% of patients adults, with strong efficacy.” treated with an alternative chemotherapy drug. • In adults, patients treated with CAR-T were 2.5 times more likely to survive for two years post treatment than patients treated with conventional treatment options (for example, most common in non-Hodgkin’s lymphoma).
Notes: Scientific references are available on request. 17 | The Pathway to CGT Adoption in Ireland
Insights from Key Cancer Opinion Leaders CAR-T is currently unavailable in Ireland, resulting in patients travelling and Patient abroad for treatment, putting significant strain on patients and their families Advocacy Groups
Patient journey to CAR-T treatment on the Treatment Abroad Scheme20 “The CAR-T centre in London won’t accept Irish patient travels Patient a patient unless they Irish patient travels abroad for eligibility abroad for second time monitored in have assessed them assessment and leukapheresis for CAR-T infusion Ireland themselves. This means families have to travel abroad twice, to be assessed and to receive treatment.”
“We are sending children Patient referral Eligibility Conditioning CAR-T creation to the UK for CAR-T Leukapheresis CAR-T infusion Monitoring and entry Assessment chemotherapy and expansion therapy through the Patient fails Patient flies Patient’s white Patient undergoes CAR-T encoding CAR-T cells are Patient returns treatment abroad scheme. second line abroad to undergo blood cells conditioning genetic material administered to to Ireland post- This takes a huge toll on cancer treatment pre-treatment (T-cells) are chemotherapy is transferred the patient abroad infusion, and is the families of critically and qualifies for eligibility separated from while cells are via viral vector. via an intravenous closely monitored ill children. The last CAR-T treatment. assessment their blood in a processed CAR-T cells are infusion with a long-term thing these parents Patient is referred process called then expanded follow-up plan want to do is fly with an to a CAR-T leukapheresis and immunocompromised physician are shipped to a child.”
manufacturing
facility
T-cells are frozen and shipped to a lab to be re-engineered, reproduced, frozen again and flown back to treatment centre
Source: McKinsey & Company (adapted to Irish situation), Interviews with Key Opinion Leaders and Patient Advocacy Groups. 18 | The Pathway to CGT Adoption in Ireland
Degenerative Diseases: Inherited Retinal Diseases Gene therapy for the treatment of inherited retinal diseases has been approved in Europe for the treatment of inherited retinal diseases, stopping disease progression and preventing patients from going completely blind
Overview Clinical Efficacy Patient Impact
Inherited retinal diseases MLMT Pass Rate; Change in MLMT Score, Pre v. Post Patient Experience (IRDs) are a group of rare eye Treatment21, 22 No one in the control • Patient interventions have historically been supportive, such as diseases caused by gene group (i.e. group not visual aids, therapy and alterations to a patient’s living situation. mutations, resulting in the 9x better outcome 100 treated with Gene with Gene Therapy progressive loss of vision, with 100% • Gene therapy is a one-time treatment, adding a working gene can Therapy) passed the many leading to total blindness. 80 1.8 successfully halt the progression of the disease. MLMT test While there are a vast number 60 of possible IRDs, Retinitis 65% Views of Key Opinion Leaders and Patient Advocacy Groups Pigmentosa, Usher Syndrome 40 and Stargardt Disease are Views“The standardof Key Opinion of care Leadersfor these andpatients Patient has Advocacymoved from Groups handing on some of the most prevalent 20 thethem patient a cane, experience to being able to stop the disease in its tracks.” IRDs in Ireland. 0% 0.2 0 “Currently, there is nothing comparable to gene therapy available. Cell and Gene therapies MLMT Pass Rate Change in MLMT Score The current standard of care is maintenance and attempting to have been approved by the Normal Vision slow the progression of the disease with assistive technology and European Medicines Agency Intervention Group (i.e. Group treated with Gene Therapy) devices.” for the treatment of vision Visually Impaired Control Group disorders. “The younger a patient gets treated the better, as we can stop the progression of the disease.” • A multi-luminance mobility test (MLMT) is used to assess visual interventions. “Patients in Ireland should have the same access to these • 65% of patients who received the gene therapy passed the test, treatments as patients in the UK and other European countries.” as opposed to 0% of the control group. For a group with normal vision, the pass rate was 100%. • Gene therapy resulted in a 9x better outcome than standard treatment. 19 | The Pathway to CGT Adoption in Ireland
Neurological Diseases: Spinal Muscular Atrophy SMA is a rare, genetic neuromuscular disease caused by a lack of a functional SMN1 gene. Disease-modifying therapies enhance SMN protein production
Overview Clinical Efficacy Patient Impact
Spinal Muscular Atrophy (SMA) Survival Rate of SMA Type 1 Patients - With Gene Therapy vs. Patient Experience with Gene Therapy is a rare, genetic neuromuscular Without26,39 • Historically there was no medical treatment for SMA, but this disease caused by a lack of a changed in April 2017 when the European Medicines Agency functional SMN1 gene, resulting in 1.0 granted marketing authorisation for a drug. the progressive and irreversible loss With treatment of motor neurons, affecting muscle • Since then, further drugs have been developed specifically functions, including breathing, targeting SMA. These treatments aim to arrest further declines swallowing and basic movement. 0.8 in muscle weakness. Type 1 accounts for 60% of SMA • A significant portion of patients have even experienced diagnoses. Untreated infants with 0.6 improvements in motor milestone measurements. SMA Type 1 will never achieve normal developmental milestones, Views of Key Opinion Leaders and Patients like sitting without support. They also 0.4 experience difficulty breathing and “We must be able to identify rare diseases earlier in children. swallowing, poor head control and Natural History Enhanced newborn screening is vital.” Permanent Ventilation severe muscle weakness. 0.2 Probability of Survival without Probability If left untreated, SMA Type 1 leads to death or the need for permanent 0.0 ventilation by the age of two in 0 20 more than 90% of cases.23 Age (Months)
Source: Novartis, AveXis Inc., World Health Organisation, Interviews with Patient Advocacy Groups, Key Opinion Leader Interviews 20 | The Pathway to CGT Adoption in Ireland
Haemophilia Gene therapy aims to be a one-time treatment for haemophilia. Patients will no longer be required to inject themselves with blood-clotting factor multiple times weekly
Overview Clinical Efficacy Patient Impact
Haemophilia is an inherited Gene Therapy in Adults with Severe Haemophilia A; Preliminary Current Patient Experience vs. Gene Therapy Experience blood disorder in which the Data - Phase Two Clinical Trial Results27, 28 • Patients with severe haemophilia inject themselves with clotting blood does not clot properly. 150 factor two to three times per week. Gene therapy aims to be a one- This lack of clotting factor Average blood-clotting time treatment. causes people to bleed for 125 factor level of patients longer than normal after an treated with a one-time Normal blood • Haemophilia patients treated with gene therapy describe it as injury and means that they are 100 dose of gene therapy, clotting factor having given them a “normal life”, no longer requiring multiple at increased risk of bleeding after almost one year level is between injections per week, a significant reduction (and elimination in many cases) of bleeding episodes and an ability to live a more active internally, inside the joints or 75 50% - 150% the brain. lifestyle31. 68% 50 • Gene therapy recipients have become more active and started Haemophilia predominantly playing sport which they have been discouraged from doing their affects men, accounting Mild 25 whole lives. for 89% of the haemophilia haemophilia:
population26, with Haemophilia % Blood Factor Clotting Level 5% >5% to 40% 0 1% Views of Key Opinion Leaders and Patient Advocacy Groups on A (HA) and B (HB) being the the current patient experience most common forms. Patients 48 Moderate Severe weeks post haemophilia haemophilia treatment without without “The current treatment is a huge burden to patients. Parents of There are a number of ongoing treatment treatment children with haemophilia have to contend with the stress of giving clinical trials evaluating gene their children an intravenous injection twice a week, along with all therapy as a treatment for • Almost one year after receiving gene therapy, patients blood other parenting tasks. It’s not easy.” haemophilia, and preliminary clotting level was the same as a person without haemophilia, data looks very promising. and they had experienced no bleeding episodes. “The big advantage of gene therapy is freedom from constant • Even a small increase in blood clotting factor can make a tethering to the hospital.” significant improvement to patients’ lives, reducing bleeding episodes and hospital visits.
Source: Centre for Disease Control and Prevention, ASH Conference, Journal of Thrombosis and Homeostasis, Patient Preference Adherence, Interviews with Key Opinion Leaders and Patient Advocacy Groups 21 | The Pathway to CGT Adoption in Ireland
Patient Perspective
Les and Lynda Martin know the pain “We want Cathal to be among the last to of losing a child. The Wicklow couple’s die of MLD and Ciarán to be among the youngest son, Cathal, died at just six after last to be disabled by it,” says Les. “The spending four years battling metachromatic cost of treatment in Ireland would be small leukodystrophy (MLD), a rare disease that compared to what it costs the State to attacks the nervous system. diagnose the disease, send patients abroad and support parents who have to give up In the same week Les and Lynda were their jobs to become full-time carers.” told Cathal had the terminal disease, they found out that their one-year-old son Ciarán Along with Lynda, Les is campaigning for had it too. “It was a brutal and traumatic enhanced blood screening for newborns. experience,” says Les. Newborns are screened for just eight diseases in Ireland. In the US, the number is But for Ciarán, now four, there was hope. 35. Italy recently increased the number from He was accepted for an experimental gene four to 48. therapy in a hospital in Italy. “We must be able to identify rare diseases With the help of the Treatment Abroad earlier in children. Enhanced newborn Scheme and fundraising, the couple moved screening is vital. We should figure out a to Italy in 2017 with their daughter, Holly, way to reimburse gene therapies in Ireland. and two sons. They lived there for eight MLD is certain death. Gene therapy is a months while Ciarán underwent treatment. solution,” says Les.
The therapy involved extracting bone marrow and stem cells and inserting a gene into the material’s genetic code to produce the enzyme that Ciarán lacked. They then re-introduced the engineered genes into his body. Ciarán’s body now produces this vital enzyme. The disease was stopped, although it had already caused brain and nerve damage. Ciarán is using ortho- therapeutics and a frame to walk now. “My wife and I became full-time carers. But Ciarán is doing well. Gene therapy is a game-changer,” says Les. 22 | The Pathway to CGT Adoption in Ireland
Patient Perspective
Her parents first had concerns about Now, Evelyn is two-and-a-half. She is a Evelyn’s vision when she was a month happy and determined girl. She experiences old. She didn’t appear to track objects or frustration and distress with her visual fix her gaze on their faces. At six weeks, impairment. When her parents collect her the concerns were validated. Evelyn from crèche, she is always by the window. was referred to paediatrics and then to She always seeks the light. ophthalmology. At 11 weeks old, Evelyn was diagnosed with a severe visual impairment But without the window light, Evelyn can’t most likely caused by an inherited retinal see the toys or the other children. She dystrophy due to a mutation in the RPE65 has memorised her environment. She can gene. move around safely only because of that. If something is out of place, she will bump Her parents kept everything going for into it. Her explored world is necessarily Evelyn’s then four-year-old brother. But small. it was hard. They were told all the things she would never do - play team sports Her parents hope that one day a treatment or drive. She might not be able to go to a will be available that will help. In the mainstream school, she might have to move meantime, they get on with their lives and, to Dublin to be close to a specialist school, against the odds, Evelyn is getting on with her parents were told. hers with the help of the people she loves.
They wondered whether she would ever see their faces, or her own face.
How would they ever explain this to her adoring older brother?
At six months the genetic diagnosis was confirmed. But there was hope through gene therapy. 23 | The Pathway to CGT Adoption in Ireland Section 3: Cell and Gene Therapy Adoption and Reimbursement Options
• The Current Drug Approval Process in Ireland and Challenges from a CGT Perspective • The Economic Case for Cell and Gene Therapies • Reimbursement Models used in other European Countries • Recommendations to Improve the Cell and Gene Therapy Landscape in Ireland 24 | The Pathway to CGT Adoption in Ireland
The Current Drug Approval Key Challenges of Applying the Process in Ireland Existing HTA Process to CGTs Health • There may be an over-reliance on measures such The HSE is responsible for decisions regarding the reimbursement of new 1 Technology as overall survival data in assessment. Data like drugs. The Corporate Pharmaceutical Unit (CPU) of the HSE is advised Assessment this will not be available for many years for most can be too by the National Centre for Pharmacoeconomics (NCPE) in assessing the CGTs. Greater acceptance of validated alternative narrow or intermediate endpoints across disease areas clinical effectiveness and value for money of new medicines. Long timelines should be incorporated, alongside assessment of may cause issues for patients with fast progressing illnesses, where rapid conventional evidence. treatment is essential. • The HTA process does not capture the full scope of benefits from CGTs. Patients and clinicians 32 High-level drug reimbursement process should have the chance to participate in the HTA process. This can help to incorporate perspectives Drug receives marketing authorisation from the • The HTA aims to combine on disease severity, unmet medical need or HPRA or the European Medicines Agency (EMA) a clinical assessment of the preferences for potentially curative therapies that drug along with an economic may otherwise not be captured by the QALY. evaluation. • This has been acknowledged in Scotland and • An incremental cost effectiveness England. Scotland has introduced Patient and Four week “Rapid Review” ratio (ICER) is established for all Clinical Expert (PACE) advisors and England has new drugs relative to existing Highly Specialised Technology (HST) assessments. standard of care. 2 Insufficient • The majority of CGTs do not have long-term • A new medicine which is more long-term efficacy data to demonstrate the long-term effects Full formal Health Technology Assessment efficacy effective and less expensive that these therapies are likely to have, negatively (HTA) data than current options will impacting the HTA outcome for CGTs. generally be recommended for • Outcomes-based payments would protect the HSE reimbursement. from the risk of CGT effects diminishing with time. Appraisal report outlining NCPE recommendations is sent to the HSE CPU • A new medicine which is more Small • Many CGTs treat rare diseases, with small patient effective and more expensive 3 patient populations. Low patient populations may be than current options will likely populations under-represented in clinical and health related not be recommended for quality of life data for a HTA. reimbursement. CGTs generally HSE makes a decision on drug reimbursement The use of • In rare diseases, it is often unethical to conduct fall into this category. 4 single-arm a randomised controlled trial (RCT) where the Source: National Centre for Pharmacoeconomics, Interviews with Key Opinion Leaders and Patient Advocacy clinical trials medicine demonstrates potential to cure a disease Groups, PwC Research with no existing effective treatment. RCTs are preferred for health technology assessments. Note: QALY or quality-adjusted life-year is a measure of disease burden, including both the quality and the quantity of life lived. It is used in economic evaluation to assess the value of medical interventions 25 | The Pathway to CGT Adoption in Ireland
The Economic Case for CGTs in Ireland Although the upfront costs of CGTs are considerable, they have the potential to significantly reduce the long-term direct and indirect costs of chronic treatment for certain illnesses, as well as significantly improve patient outcomes Direct and Indirect Costs of Conventional Treatment vs. Cell and Gene Therapy Criteria Cancer Spinal Muscular Atrophy (SMA) Type 1 Severe Haemophilia • If all available treatment options are exhausted, • Treatment for a severe haemophilia patients can currently be referred for CAR-T patient costs c. €130,000 per year*,34. Life • Healthcare systems are currently designed to pay for chronic treatment over Direct treatment abroad at the full list price of the expectancy of a man in Ireland is 80.4 years. many years or decades. In Europe, the cumulative estimated healthcare costs per costs treatment. This is an upfront, once-off payment, Total lifetime cost of severe haemophilia A is child with SMA ranges between €2.5 to €4 million.33 with no rebates should a negative outcome €10.45 million. Treatment of haemophilia in occur. the US costs circa. $500,000 per year.35 • The necessity of a permanent carer is a major component of healthcare costs. Current • Indirect costs of €6,000 per year, due to loss • In most cases, the Treatment Abroad Scheme HIQA guidelines enable gene therapy for SMA to include societal costs as a approach Indirect of productivity, absenteeism, disability and does not cover travel or subsistence expenses, scenario analysis, taking into account: Patients’ potential income if patients could costs OTC medicines. Total lifetime indirect costs imposing financial pressure on families. participate in the workforce in the future; Lost family income due to SMA-specific is €482,400. care provided by the family; Direct non-medical costs. • Patient required to self-inject two to three • Travelling abroad with a severely compromised Patient • If left untreated, SMA Type 1 leads to death or the need for permanent ventilation times per week. Bleeding episodes are rare, immune system puts patients and their families impact by the age of two in more than 90% of cases. but on occurence, require hospital visits and under unnecessary anxiety and hardship. physiotherapy. • Through negotiations the HSE could pay less than the list price of the treatment, as a once • In the long term, disease-modifying treatments such as gene therapy could offer • Undetermined, however gene therapy likely Direct off cost. Outcomes based payments could be a significantly lower treatment cost compared to currently available therapies, to cost in excess of €1 million, with the aim costs agreed, with rebates given should a negative resulting in savings to healthcare systems..35 of being a one-time treatment. outcome occur.
• Indirect travel costs will be eliminated if • Gene therapy could halt the progression of the disease. The long-term indirect • Likely to be low, gene therapy recipients treatment is delivered in Ireland. cost of a patient’s care depends on the severity of the disease at treatment. SMA Cell and Indirect have experienced no bleeding episodes, has substantial effects on the families and carers of infants with the disease, Gene costs • CAR-T results in lower indirect costs compared resulting in less absenteeism from work and including the impact of caring for the patient, the need for specialist equipment Therapy with costs prior to treatment, with fewer and no hospital visits. shorter hospitalisations and less A&E visits33. and the ongoing emotional, social and financial impacts. • Treatment in a familiar setting, with regular • No requirement for IV injections, no bleeding • With early treatment, preferably identified through newborn screening, patients Patient medical team will reduce unnecessary anxiety. episodes and no emergency hospital visits. could have the possibility to go on to live a normal life and hit standard impact Reduced requirement to travel can result in Patients describe gene therapy as having developmental milestones, with limited personal care and healthcare required improved aftercare. given them a “normal life”.
Note: *Financial cost of haemophilia in the UK, closest resemblance to Ireland. Source: American Journal of Managed Care, National Centre for Pharmacoeconomics, The Irish Times, International Journal of Environmental Research and Public Health, Orphanet Journal of Rare Diseases, National Centre for Pharmacoeconomics. 26 | The Pathway to CGT Adoption in Ireland
Reimbursement and Funding Benefits of Novel Payment Models for CGTs Models CGTs present a challenge to standard reimbursement models. Novel payment Novel payment models allow models would allow the health service to share the risk with industry. Share 1 the risk for risk-sharing between the HSE and industry. Payment models currently in use for CGTs36 Increase Budget challenges (particularly post-COVID-19) Payment Model Key Features Locations Enablers 2 speed of access could further delay Irish Payment is spread over patients’ access to innovative Annuity-based a number of years in • Italy medicines. Instalments-based model - staged a pre-agreed payment payments could accelerate • Spain payments plan, linked to individual access to CGTs for patients in patient outcomes Ireland. Future price reassessment based on Encourage CGTs require extensive Coverage longer-term follow up • France research and development, with evidence 3 medical data from pivotal trials resulting in their considerable development • United Kingdom Recording innovation and real-world use in of patient cost. Novel schemes can patients outcomes over reward and encourage time Rebates from medical innovation while pharmaceutical company reducing the risk for the payer. Outcomes-based to government based • Germany rebates on individual patient outcomes
Instalments over several Blended annuity- years, with outcomes style payments with • United States based rebates based on rebates patient outcomes
Source: Journal of Market Access & Health Policy. 27 | The Pathway to CGT Adoption in Ireland
Key Challenges to CGT Adoption Amendments to the current assessment process, along with investment in data, resources and capabilities, would allow Ireland to implement new payment models and adopt CGTs
Assessment Reimbursement Models
• The current HTA process has limitations in considering the true value of • The current reimbursement structures are not set up to allow for one-time treatments or treatments with curative intent. investment in one-time, high value treatments such as CGTs due to traditional payment models and single year healthcare budgets. • CGTs are relatively new and therefore often have insufficient long-term data. Furthermore, low patient populations and the use of single-arm • This has resulted in delayed access to innovative medicines for Irish trials complicates preparing HTAs. patients and creates a risk that the HSE could end up paying a higher price for cell and gene treatments abroad. • There is a lack of a transparent accountability framework with clearly defined timelines for the post-assessment process, particularly regarding commercial negotiations between manufacturers and the HSE.
Data Infrastructure Capabilities and Resources
• The Irish healthcare service lags in digitisation, resulting in gaps in the • In certain therapeutic areas, Irish hospitals are prepared and ready to ability to sufficiently track patient outcomes for the use of novel payment adopt CGTs – for example, CAR-T in Crumlin Children’s Hospital and in models. St James’ Hospital, Dublin. • Existing health data sources include registries, hospital and patient • Other therapeutic areas require investment in capabilities and records, claims data, health, demographic and socio-economic resources to ensure readiness for delivery of CGTs upon approval and databases - but these remain fragmented, lacking scale, robustness and reimbursement. detail to support outcomes measurement. • With CGTs increasingly being administered abroad, Irish healthcare staff • Lack of health data collection and use reduces Ireland’s ability to are losing the opportunity to further their skills in the area. measure cost-effectiveness and ensure value for money for treatments. 28 | The Pathway to CGT Adoption in Ireland
Recommendations to ensure Ireland does not fall further behind in delivering CGTs
A CGT adoption policy, guided by a White Paper Introduce novel reimbursement models to led by the Department of Health, which draws Recommendation ensure broad access and value for money for together proposals for tackling the related strands of Irish patients 1 assessment, access and reimbursement 2
Actions required by:
• Document pathways for post-HTA reimbursement and guidance on the most • Begin work to implement new reimbursement models that build on appropriate path per therapy (Beneluxa vs national) outcomes data as a primary enabler • Explore options to reform the current reimbursement approach for the long • Evolve the current reimbursement decision-making process to account term to allow for high-tech therapies to be provided to Irish patients in a for: business-as-usual manner Government – The breakthrough nature of these therapies, and • Provide clear timelines and accountabilities for the assessment of CGT – The developing picture on long-term patient outcomes medicines • Implementation of novel contracting approaches should be considered • Government to consider and set an ambition and vision for new therapies to ensure value for money for the State when deploying these treatments availability in Ireland
• Conduct working sessions with Government to define a CGT assessment, • Draw on learnings from payment models in place for specific CGTs in access and reimbursement White Paper and subsequent roadmap other European countries • Ensure buy-in and agreement from all parties on key elements of the policy to • Industry to explore funding research into evolving current frameworks for Industry ensure the best outcome for patients is achieved funding and reimbursement • Discuss and agree appropriate payment models for CGT with the HSE • Adequately share the risk of failure of these treatments with Government
• Patient representatives attend working sessions to ensure patient voice is • Where possible, allow Government to use available data to assess Patient Advocacy heard and incorporated into CGT roadmap effectiveness of CGT treatments Groups
Recommendations should be implemented in parallel where possible 29 | The Pathway to CGT Adoption in Ireland
Recommendations to ensure Ireland does not fall further behind in delivering CGTs
Improve the data infrastructure for key Continue to invest in facilities and staff while disorders likely to benefit from CGTs in the ensuring training and engagement with Recommendation short term and start planning for a broader clinicians and patients to allow for a smooth 3 rollout in other areas in the medium term 4 national rollout of CGTs
Actions required by:
• Acknowledge that registries can form the basis for measuring outcomes in • Work with CGT manufacturers to define the core criteria required in Irish reimbursement in the short term hospitals to deliver CGTs • Inventory existing registries and audit for potential use for outcomes • Support the creation of centres of excellence for CGTs to ensure the tracking purposes development of sufficient expertise in Ireland Government • Invest to upgrade current registries and tracking projects to scale • Provide funding/support for healthcare providers in Ireland looking to be nationally and put them on a sustainable basis, in collaboration with certified to deliver CGTs industry and patient groups • Invest in additional services and capacity, with greater distribution of • Expand cooperation across Europe to ensure sufficient data is collected in centres of excellence a standardised, high-quality way to allow for the assessment of CGTs
• Industry should be encouraged and incentivised to co-invest with State • Work with Government to define the key requirements to deliver CGTs in bodies - for example, SFI and HRB - in clinical trials, real-world data Ireland collection and data registries through funding, standard setting and Industry • Produce a guide outlining the full suite of requirements necessary to investments in data platforms and storage infrastructure (for example, SFI provide each CGT, allowing hospitals to prepare for delivering treatments Enterprise Partnership Model) upon reimbursement
• Collaborate with and support the Government in its efforts to improve • Work with industry and Government to create CGT resources for patients Patient Advocacy tracking of patient outcomes in multiple languages Groups • Commit to continuing registries in the long term where necessary for • Cover a comprehensive explanation of CGTs, eligibility, the process of evaluating the outcomes of CGT treatment receiving CGTs and the long-term-follow-up, potential adverse events, etc.
Recommendations should be implemented in parallel where possible 30 | The Pathway to CGT Adoption in Ireland
Challenges to Implementing Recommendations Implementing the recommendations in this report, will be an ambitious undertaking. Inevitably, a number of challenges will arise throughout the process.
Recommendation Challenge to Implementation Risk of Occurrence
Issues aligning on key criteria for assessment and access to CGTs Medium
1 Assessment Insufficient resources to meet agreed timelines for assessment Low Lack of clarity over roles and responsibilities. Government must take ownership of creating the CGT access Low and assessment framework
Challenges agreeing appropriate share of the risk for industry and Government Medium Reimbursement Models 2 Current lack of ability to track outcomes data presents a key obstacle to implementing outcomes-based Medium payment schemes in the short to medium term
Striving for a fully formed data solution before implementing novel payment schemes rather than working Medium with the current data available to achieve results sooner
In some therapeutic areas there will be many stakeholders- Government, industry, clinicians and patients- all with different objectives and requirements. Issues are likely to arise unless stakeholder management and Medium Data Infrastructure collaboration are prioritised 3 GDPR could present a key challenge unless the intentions for and use of data are specified from the Medium beginning
Ensuring there is adequate dedicated time for healthcare professionals to become certified in administering Medium CGTs and caring for patients who have received them
4 Expertise and Resources Challenges ensuring broad geographic coverage of CGT delivery Medium 31 | The Pathway to CGT Adoption in Ireland
Contributors to Report A number of key opinion leaders and patient advocacy groups contributed to the production of this report. PwC would like to thank all parties for their contribution.
Authors Supporting organisations
Garrett Cronin Shane Gannon and companies Partner, Operational Effectiveness Director, Pharma and Life Science Consulting Consulting Office: +353 1 792 8807 Office: +353 1 792 6308 [email protected] [email protected]
Kieran Little Orla Kennelly Director, Strategy Consulting Associate, Strategy Consulting Office: +353 1 792 5782 Office: +353 1 792 6407 [email protected] [email protected]
PwC conducted a number of interviews to support this report, including: • Five interviews with Key Opinion Leaders in a range of medical fields • Four interviews with Patient Advocacy Groups Thank you to all interviewees for your invaluable contribution. 32 | The Pathway to CGT Adoption in Ireland
Appendix 33 | The Pathway to CGT Adoption in Ireland
The industry view: Protecting IP for New Treatments Development
In November, the European Commission published its proposed Pharmaceutical Strategy for the European Union. The biopharmaceutical industry broadly supports the Strategy. We share the European Commission’s vision for a healthier society based on prevention and innovation. We, too, want to sustain investment and jobs in this sector, tackle unmet medical needs, address anti-microbial resistance, improve patients’ access to new medicines and raise standards of healthcare. Ireland, with is high-performing clusters of leading About 300,000 people in Ireland are affected by a rare The Strategy has several initiatives to help realise a shared biopharmaceutical companies spread across the regions, disease. There are over 300 million people living with one or healthcare vision. But, in some key areas, the Strategy will is an exemplar for innovation. We should be a leading voice more of over 6,000 rare diseases around the world. About cede ground in medicines innovation rather than reclaim it in Europe in supporting the biopharmaceutical innovation 72% of rare diseases are genetic and 70% of those start in for Europe. Some measures will limit, rather than strengthen, agenda, especially for Europe as a location for new, high- childhood. A disease is defined as rare in Europe when it our ability to tackle unmet medical needs. At the same time, value research and manufacturing investment, the protection affects fewer than one in 2,000 people. the measures will fail to improve new medicines availability, of intellectual property (IP) rights to catalyse the development access and affordability for European patients. of new medicines, and the adoption of innovative new If IP incentives are weakened, new medicines development therapies equitably across countries. will slow, leaving medical needs, in both children and adults, COVID-19 has underlined the importance of innovation in unmet. Because patient numbers are often small, unless vaccines, medicines and healthcare technologies. We favour Two key IP rights are at risk under the European originator companies take on the research and development creating faster, more equitable and sustainable access to Commission’s plans - the Paediatric Medicines Regulation, project no one else will. Ireland, at political and official new medicines and fostering an innovation ecosystem that adopted in 2007, and the Orphan Medicinal Products levels, must raise its voice on the importance of protecting can respond to unmet medical needs. That effort will require Regulation, adopted in 2000. Under the Paediatric Medicines IP incentives, placing ourselves firmly in the pro-innovation a new type of dialogue - a multi-stakeholder High-Level Regulation, over 260 medicines have been developed for camp in Brussels. Forum on Better Access to Health Innovation. children, with an increase of 50% in clinical trials between 2007 and 2016. Under the Orphan Medicinal Products Regulation, more medicines have arrived for rare diseases. In 2000, there were just eight orphan medicines. In 2018, there were 164. Newborn Screening: 1 heel prick test has the potential to diagnose 50 diseases SIGNIFICANT VARIATIONS EXIST ACROSS COUNTRIES More than Country Rankings
Screening for...
49 29 19 9 2 Italy 48 Diseases 1test 50diseases Austria 29 Diseases Number of diseases screened at birth as part of a national testing programme Disease Abbreviations (used overleaf...) Portugal 29 Diseases ALD Adrenoleukodystrophy IBG Isobutyrril-CoA dehydrogenase Poland 28 Diseases ASA Argininosuccinic aciduria deficiency Hungary 26 Diseases ARG Arginase deficiency IVA Isovaleric acidemia A-T Alpha Thalassemia LCHAD Long-chain hydroxyacyl CoA Sweden 26 Diseases BIOPT (BS) Biopterin cofactor dehydrogenase deficiency Norway 25 Diseases biosynthesis deficiency MADD Multiplex acyl-CoA BIOPT (REG) Biopterin cofactor dehydrogenase deficiency Netherlands 24 Diseases MAL Malonic aciduria regeneration deficiency Finland 23 Diseases BKT Deficit of Beta-ketothiolase MAT Methionine adenosyltransferase B-T Beta thalassemia deficiency Germany 20 Diseases BTD Defect of biotinidase MCAD Medium-chain acyl CoA CACT Carnitine / acyl-carnitine dehydrogenase deficiency Estonia 20 Diseases translocase deficiency MCD Multiple carboxylase deficiency Slovenia 20 Diseases CAH Congenital Adrenal Hyperplasia MLD Metachromatic Leukodystrophy Cbl A Methylmalonic acidemia (CblA) MMA Vitamin B12 deficiency Czech Republic 19 Diseases MPS I Type I mucopolysaccharidosis Cbl B Methylmalonic acidemia (CblB) Denmark 18 Diseases Cbl C Methylmalonic Acidemia with M / SCHAD Short / medium chain Homocystinuria (CblC) 3-OH acyl-CoA dehydrogenase Slovakia 13 Diseases deficiency Cbl D Methylmalonic Acidemia with Switzerland 10 Diseases Homocystinuria (CblD) MSUD Maple syrup urine disease CF Cystic Fibrosis MTHFR Homocystinuria due to Belgium 9 Diseases CHT Congenital Hypothyroidism MTHFR deficiency MUT Methylmalonic acidemia (Mut) CIT Citrullinemia type I UK 9 Diseases ORN Hyperornithinemia with Gyrate CIT II Citrullinemia type II (Citrine Atrophy of Choroid and Retina Croatia 9 Diseases deficiency) PA Propionic Acidemia CPT I Carnitine palmitoyl-transferase Ireland 8 Diseases PKU Phenylketonuria (L) deficiency POMPE Pompe Disease Spain 7 Diseases CPT II Carnitine palmitoyl-trans- SAHH Deficit of S-adenosylhomo- ferase II deficiency France 6 Diseases cysteine hydrolase CUD Lack of carnitine transport SCD Sickle cell disease Latvia 6 Diseases EXP Short-chain acyl CoA SCID Severe combined dehydrogenase deficiency immunodeficiency Greece 4 Diseases FABRY Fabry Disease SMA Spinal Muscular Atrophy Lithuania 4 Diseases GA I Glutaric acidemia type I TFP Deficit of the trifunctional protein GA2 Glutaric acidemia type II TYR I Type I tyrosinemia Bulgaria 3 Diseases GAL Galactosemia TYR II Tyrosinemia type II Cyprus 2 Diseases GALK Galactokinase deficiency TYR III Tyrosinemia type III GNMT Glycine N-methyltransferase VLCAD Very long chain acyl CoA Romania 2 Diseases deficiency dehydrogenase deficiency G6PD Glucose-6-phosphate 2MBG 2-Methyl butyryl-CoA dehydrogenase dehydrogenase deficiency HCU Homocystinuria (CBS 2M3HBA 2-Methyl 3-hydroxy butyric deficiency) aciduria RESEARCH PUBLISHED MARCH 2021 HMG 3-Hydroxy 3-methyl glutaric 3MGCA 3-methyl glutaconic acids aciduria 3MCC Deficit of 3-Methyl H-PHE Benign hyperphenylalaninemia crotonyl-CoA carboxyalsi Research supported by Novartis AG 35 | The Pathway to CGT Adoption in Ireland
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